The objective of the proposed research project is to define possible controls for DNA biosynthesis during normal and abnormal growth. 1) The interactions of enzymic and non-enzymic factors in the elongation step of DNA replication will be studied. We will characterize these components of the DNA synthesizing machinery and determine their mechanism(s) of action. 2) The basis for the molecular heterogeneity of DNA polymerase alpha in mammalian cells will be investigated. We will ascertain the possible physiological significance of this heterogeneity. 3) The relationship of chromatin associated to non-chromatin associated DNA polymerase alpha will be studied. We will ascertain if DNA polymerase alpha is translocated to the nucleus as a pro-enzyme.